POS1509 CLUSTER ANALYSIS FOR THE IDENTIFICATION OF CLINICAL PHENOTYPES AMONG ANTIPHOSPHOLIPID ANTIBODIES ASSOCIATED ADVERSE PREGNANCY OUTCOMES: A BASED ON A 13-YEAR LONGITUDINAL COHORT STUDY
Authors: Y. Long, J. Zhao, M. LI, X. Tian, X. Zeng
Journal: Annals of the Rheumatic Diseases (2023)

Background Antiphospholipid antibodies (aPLs) are the leading causes of adverse pregnancy outcomes (APO). Women with persistently aPLs positive present heterogeneous clinical manifestations and APO, suggesting different pathogenic mechanisms behind each feature [1] . Objectives We applied cluster analysis to identify specific phenotypes among aPLs-positive women with APO to manage risk stratification during pregnancy and improve prognosis. Methods This was a prospective study of persistent aPLs-positive women cohort to Peking Union Medical College Hospital between July 2009 and February 2022. Baseline demographic characteristics, clinical manifestation, previous pregnancy history and antibodies profiles were recorded. We identified APO as early miscarriage (EM) before 10 weeks, late miscarriage (LM), fetal death at/after 10th week, stillbirth, pregnancy induced hypertension (PIH), pre-eclampsia, eclampsia, HELLP, decreased amniotic fluid, fetal growth restriction (FGR) and premature. Hierarchical cluster analysis and Chi-square test and Fisher’s exact test were performed. Results A total of 209 patients with 477 pregnancies were enrolled in this study. the mean maternal age was 31.32 ± 6.61years. During the follow-up, 78 new-onset pregnancies were occurred in 68 patients. Anti-β2glycoprotein I antibody (β2GPI) was the most frequently found in persistent aPLs-positive women. IgM subtype was accounted for 24.40%, and IgG accounted for 34.00%. Half of patients were positive for anticardiolipin antibody (ACL) and lupus anticoagulant (LA). EM accounted the highest proportion of APOs, with 184 (38.75%.) occurrences. This was followed by LM with 131 (27.6%) pregnancies. The live birth rate improved from 17.29% before enrollment to 75.64% dramatically. Fifty-eight (14.54%) PIH events occurred in 399 pregnancies, 24 of which progressed to preeclampsia or eclampsia. Three clusters among 209 patients were identified. Cluster 1 (60 patients, 28.71%) consisted mainly of women with systemic lupus erythematosus (SLE) and major presented aPLs IgG subtype. Women in this group had the significantly highest incidence of PIH and LM events. Cluster 2 (70 patients, 33.49%) presented IgG subtypes with the highest percentage of placenta insufficiency (PI). All subjects in the cluster had moderate lupus clinical characteristics. Cluster 3 (79 patients, 37.80%) showed the highest prevalence of IgM subtype of β2GPI and ACL (87.34%,36.71%, respectively). Women in this cluster suffered highest frequency of EM (62.03%), while the lowest rate of late term APO among the three groups (PIH, 13.92%; LM, 34.18%). After standard treatment, it is noteworthy that the live birth rate of cluster 1 patients was only 69.2%, much lower than the other two clusters. Hematoxylin-eosin (HE) staining of the placenta also showed severe foci of infarction and calcification, and the vacuolar degeneration of placental villi stem vascular endothelial cells in cluster 1 (Figure 1). Conclusion Our study proposes that persistent aPLs-positive women with APO have three major clinical subtypes. Cluster 1 contains patients with a predisposition to SLE. Patients in cluster 2 majorly present PI combined with aPLs-IgG subtype, while cluster 3 present EM with aPLs-IgM subtype. The individualized risk stratification assessment of these patients will help to develop different treatment strategies and improve the pregnancy outcome. Reference [1] Bouvier, S.; Cochery-Nouvellon, E.; Lavigne-Lissalde, G et al. Comparative incidence of pregnancy outcomes in treated obstetric antiphospholipid syndrome: the NOH-APS observational study. Blood 2014 , 123 , 404-413, Acknowledgements: NIL. Disclosure of Interests None Declared.